Claudia Calogero
Enrico Lombardi- Pediatric Pulmonary Unit, “Anna Meyer” Pediatric University Hospital, Florence, Italy
Lung function is an important tool in the diagnosis and monitoring of patients with asthma at all ages. Airway obstruction is a typical feature of asthma and it can be assessed with several lung function techniques. Spirometry, respiratory resistance and reactance, and lung volumes are available to measure it at different ages and in children. The assessment of a bronchodilator response is always recommended to show the reversibility of the obstruction. Poor lung function is a predictor of poor asthma outcome and a low Forced Expiratory Volume in the first second of expiration percent predicted measured with spirometry, has been shown to be associated with a higher risk of having an exacerbation during the following year independently of the presence of asthma symptoms. In severe asthma lung function assessment is used to distinguish different phenotypes, children with severe asthma have worse airflow limitation prior to administration of a bronchodilator than children with non severe asthma. Airway resistance and reactance are indirect measurements of airway obstruction and they can be measured with the forced oscillation technique, which is feasible also in non-collaborative children. This technique can be more informative in discriminating patients with asthma from healthy controls and is able to indicate a more peripheral involvement of the airways. The role of this technique in severe asthma is still debated. In conclusion lung function is useful in the clinical management of children with severe asthma.
Introduction
Lung function measurements are very important in the diagnosis and monitoring of patients with asthma, especially those with severe asthma. Several techniques are available for children and adults to measure airway obstruction, which is a typical feature of asthma. Furthermore, tracking of lung function, from childhood to adulthood, has been shown in several studies, highlighting that reduced lung function at young age is associated with the development of chronic obstructive pulmonary disease (COPD) in adulthood (1–3). This article will cover the main pulmonary function techniques used in children to detect airway obstruction and their clinical utility in the diagnosis and management of severe asthma in children.
Spirometry
Spirometry indices are obtained with a forced expiratory maneuver according to the technical European Respiratory Society (ERS)/American Respiratory Society (ATS) recommendations (4). Modified acceptability criteria for spirometry in preschool children (2–5 years) have also been published (5). The Forced Expiratory Volume in the first second of expiration (FEV1) and its ratio to Forced Vital Capacity (FEV1/FVC) are considered the gold standard to assess airway obstruction in adults and children (6). These indices are sufficient to grade the severity of obstruction, which is very important in the evaluation of subjects with severe asthma. Obstruction is shown by an abnormal FEV1/FVC (< 80%) and is defined as mild when FEV1 is >70% predicted, moderate 60–69%, moderately severe 50–59%, severe 35–49%, very severe < 35% (7).
Once a baseline measure is obtained, the evaluation of the reversibility of the obstruction with the assessment of the bronchodilator response (BDR) is recommended, as this is a typical feature of asthma. A positive BDR is defined by the ERS/ATS recommendations as an increase in FEV1 ≥12% and ≥200 mL with respect to baseline after administration of 400 mcg of salbutamol given by metered dose inhaler via a spacer (7). However, it has been described by Tse et al. that in children this cut-off can be not enough sensitive to detect airway obstruction and can lead to a misdiagnosis of asthma (8), suggesting that a lower cut-off (8%) should be used in children.
Regarding the clinical utility of spirometry, the American Academy of Asthma, Allergy and Immunology states in the list of the Choosing Wisely Initiative “do not diagnose or manage asthma without spirometry”1. Also, according the most recent update of the GINA Guidelines (9) the diagnosis of asthma should be made not only based on the clinical features of the patient, such as clinical history and symptoms, but also using pulmonary function testing to detect the presence of airflow limitation. Furthermore, the NICE guidelines (10) recommend to perform spirometry in children and adults with a diagnosis of asthma to show an obstructive pattern on the test. The assessment of a bronchodilator response is also recommended to show the reversibility of the obstruction. Several guidelines on asthma also recommend to perform spirometry for monitoring asthma at each visit (10) or at least after 3 or 6 months from the beginning of treatment and on a regular basis afterwards (1–2 years) (9).
Measuring lung function is also useful as a predictor of asthma exacerbations. In the GINA guidelines (9) a low value of FEV1 is mentioned as a predictor of poor asthma outcome. In a retrospective study in children with asthma, a low FEV1 percent predicted (particularly when < 60%) has been shown to be associated with a higher risk of having an exacerbation during the following year independently of the presence of symptoms (11). Also, Schifano et al. have described in a population of 894 asthmatic children a low concordance between symptoms and lung function results and a higher grade of asthma severity was given when spirometry was taken into account (12). This is very important in children especially when a poor awareness of symptoms is detected.
Spirometry is able to measure flows at low lung volumes that are considered to be more representative of the small airways such as the forced expiratory flow between 25 and 75% of FVC (FEF25−75), at 50% of FVC (FEF50,), and at 75% of FVC (FEF75). The role of these indices in detecting airway obstruction in clinical practice is however controversial. Some authors have shown that these indices are more sensitive than FEV1 in detecting peripheral obstruction [(13)], while others have shown that they do not affect the clinical decision more than FEV1/FVC (14). For this reason, a recent ATS Technical Statement recommends that FEF25−75 should not be shown in the pulmonary function report (15).
The definition of severe asthma, according to an ERS/ATS Task Force (16), is the presence of uncontrolled symptoms despite high dose of corticosteroids and includes difficult to treat asthma and asthma resistant to therapy. Lung function assessment is necessary for confirming the diagnosis of severe asthma and to establish the phenotype. From a practical point of view, spirometry is useful in confirming the diagnosis of severe asthma in children and it should be always performed with the administration of a bronchodilator to detect airway obstruction and its reversibility. The aspect of the Flow-Volume inspiratory and expiratory loops can be also useful in the differential diagnosis of other causes of obstruction, intrathoracic or extrathoracic airway obstruction (17).
Different phenotypes of severe asthma have been described (18, 19). These phenotypes change according to age and are different in children and adults (20). Assessing airway obstruction is useful to identify the phenotypes at all age (21). Airway obstruction however, can be not present or only mild in children with severe asthma especially in between exacerbations (22–24). In respect to adults with severe asthma, children tend to have better lung function, but a greater decline overtime (25). It has been recently reported that children with severe asthma have worse airflow limitation prior to administration of a bronchodilator than children with non-severe asthma, but have similar values after BD showing an increased BDR (20).
In the TENOR Study, that included also children and adolescents, the authors have shown that acute asthmatic exacerbations can have a role in the decline of lung function, as the inflammation cascade can lead to airway remodeling and a fixed non reversible bronchoconstriction (26). In children this mechanism can be different and especially when there is eosinophilic inflammation remodeling of airways is not always present (27). Contrarily, a recent study published by Ortega et al. on lung function data retrospectively collected from the DREAM and MENSA studies on mepolizumab in severe asthmatics with eosinophilic inflammation (mainly adults with a very small proportion of adolescents), shows that a higher number of exacerbations is associated with a worsening of lung function measurements over time (28). These features can identify a more severe phenotype of asthma and each exacerbation can contribute with a loss in FEV1 of about 50 mL/year (28). The mechanism involved is hypothesized to be a reduced elasticity of the lung as a result of airway narrowing and remodeling associated to deposition of collagen.
Lung function measurements can be used to monitor response to therapy but few data are available on severe asthma in children. Deschildre et al. published data on 1 year of real life experience on 104 children with severe asthma treated with omalizumab showing an increase of 4.9% predicted of FEV1 at the end of the 12 months (29). A recent longitudinal study on lung function in severe asthma conducted in Brazil on 65 severe asthmatic patients (between 6 and 18 years of age) receiving high dose of corticosteroids showed only a small improvement of airway reversibility (FEV1 after bronchodilator) (30).
Body Plethysmography
Lung function obtained with the body plethysmography allows to measure airway resistance and lung volumes, with particular interest to Total Lung Capacity (TLC) and Residual Volume (RV). RV is a good index of air trapping and is a marker of hyperinflation when the value is greater than 120% predicted. This measure can add information to the conventional spirometry especially in severe asthmatic patients. It has been shown that 49% of children having airflow obstruction with an FEV1/FVC < 80% have a significant hyperinflation (31). Sorkeness et al. in the SARP cohort, showed that children with severe asthma were more hyperinflated and air-trapped in respect to children with non severe asthma that had normal RV and TLC (32).
Respiratory Resistance and Reactance
Airway resistance, which is an indirect measurement of airway obstruction, can be evaluated with the body plethysmograph, but its measurement requires the panting maneuver which is substantially infeasible in preschool children. Several techniques have been developed, such as the interrupter technique (Rint), the forced oscillation technique (FOT), and the measurement of specific airway resistance (sRaw) using the body plethysmograph, which are performed during tidal breathing. These techniques require only minimal collaboration and are feasible also in preschool children when spirometry cannot be performed or other techniques cannot be used. In addition to respiratory resistance, FOT offers the advantage of also measuring respiratory reactance, which can be thought of as the distensibility of the respiratory system. Technical recommendations for each technique are available (5, 33) and several reference equations have been published (34–36).
The evaluation of the bronchodilator response is also possible and different cut-off values have been reported in the literature (35, 37, 38). Those techniques, with particular regard to FOT has been suggested to be more sensitive in detecting airway obstruction because of no “deep inspiration” effect on bronchial tone that is required with a forced maneuver (39, 40).
In a study conducted from Heijkenskjold Rentzhog et al. (41), the authors showed that FOT measurements were more informative in discriminating patients with asthma from healthy controls. FOT measurements were able to indicate a more peripheral involvement of the airways. Similar results are also available form previous studies on BDR in FOT resistance measurements and spirometry in children (39, 42) and adults (43). IOS results compared to spirometry have been shown to be able to predict loss of control in a group of 54 children with asthma (44). Data from 252 children with mild to moderate persistent asthma, demonstrated that the area under the reactance curve measured with IOS, was able to detect changes in airway mechanics after weeks of treatment in respect to other oscillations indices or spirometry results (45). There are some data that show that sRaw measured at preschool age correlates with mild obstruction measured with low volumes (6), also in a recent study, although on a small number of asthmatic children, sRaw is a better indices of bronchoconstriction in respect to FEV1 after a challenge test (46).
The role of these techniques in severe asthma in children remains to be assessed and further studies are needed.
Multiple Breath Washout (MBW)
The Multiple Breath Washout technique measures the Lung Clearance Index (LCI), which is the cumulative expired volume required to clear an inert gas from the lungs, divided by FRC or the number of times the lung volume has to be “turned over” to wash out an inert gas such as nitrogen (N2) or sulfur hexafluoride (SF6). LCI is an index of inhomogeneity of ventilation and it has been demonstrated to be able to detect early lung damage in particular in children chronic lung disease such as Cystic Fibrosis (47), however it has some limits in measuring airway obstruction. In severe asthma with severe obstruction some areas of the lung can be excluded from ventilation giving a false value of LCI that can even appear within the normal range. Scond is another index measured with MBW that refers to the inhomogeneity of the conducting airways and this might be more useful in asthmatic patients. The limits of this technique are also related to the lack of extended reference equations with particular respect to the pediatric population.
Bronchial Hyperresponsiveness
Bronchial hyperresponsiveness (BHR) can be considered as the variation of the bronchial tone that can vary after exposition to different stimuli. The stimuli that can be used as provocation test can be direct (chemicals such as histamine or methacholine, or inhaled allergens) or indirect (physical exercise, mannitol, inhaled cold air or hyperventilation with dry cold air). After a brochoprovocation test a fall in FEV1 of 20 or 15%, depending on the test used, is considered as a cut off value. A maximal fall of FEV1 between 10 or more in respect to the baseline value on two consecutive measurements after a maximal effort is considered diagnostic for exercised induced bronchoconstriction (48). In children exercise testing can be very important for the assessment of asthma in the diagnostic process but also in monitoring the response to therapy, especially when exercise symptoms are reported or there is a poor perception of symptoms (9). Methacholine bronchoprovocation test is more sensitive but less specific than exercise testing in asthmatics (49).
In a prospective study Part et al, showed in 1,041 children, the CAMP Cohort, that the percent recovery index (the percent increase in FEV1 after bronchodilator) in response to a bronchial challenge with methacholine was able to predict an asthmatic exacerbation in the following year (50). In severe asthma, both methacholine and exercise tests can be used to asses BHR when the diagnosis is not clear in difficult cases (16). The role of BHR in the clinical evaluation of the child with severe asthma is debatable and it is not safe to evaluate when baseline FEV1 is low (51).
Conclusion
In conclusion, pulmonary function testing assessing airway obstruction is important in the clinical management of children with asthma and severe asthma during diagnosis, monitoring and evaluating response to treatment.
Author Contributions
All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.
Funding
This article was funded by the Meyer Foundation, Florence, Italy.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Footnotes
References
1. Krishnan JK, Martinez FJ. Lung function trajectories and chronic obstructive pulmonary disease: current understanding and knowledge gaps. Curr Opin Pulm Med. (2018) 24:124–9. doi: 10.1097/MCP.0000000000000456
2. Bui DS, Lodge CJ, Burgess JA, Lowe AJ, Perret J, Bui MQ et al. Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life. Lancet Respir Med. (2018). doi: 10.1016/S2213-2600(18)30100-0. [Epub ahead of print].
3. Belgrave DCM, Granell R, Turner SW, Curtin JA, Buchan IE, Le Souëf PN et al. Lung function trajectories from pre-school age to adulthood and their associations with early life factors: a retrospective analysis of three population-based birth cohort studies. Lancet Respir Med. (2018). doi: 10.1016/S2213-2600(18)30099-7. [Epub ahead of print].
4. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A et al. Standardisation of spirometry. Eur Respir J. (2005) 26:319–38. doi: 10.1183/09031936.05.00034805
5. Beydon N, Davis SD, Lombardi E, Allen JL, Arets HGM, Aurora P et al. An official american thoracic society/European respiratory society statement: pulmonary function testing in preschool children. Am J Respir Crit Care Med. (2007) 175:1304–45. doi: 10.1164/rccm.200605-642ST
6. Moeller A, Carlsen KH, Sly PD, Baraldi E, Piacentin G, Pavord I et al. Monitoring asthma in childhood: lung function, bronchial responsiveness and inflammation. Eur Respir Rev. (2015) 24:204–15. doi: 10.1183/16000617.00003914
7. Pellegrino R, Viegi G, Brusasco V, Crapo F, Burgos F, Casaburi R et al. Interpretative strategies for lung function tests. Eur Respir J. (2005) 26:948–68. doi: 10.1183/09031936.05.00035205
8. Tse SM, Gold DR, Sordillo JE, Hoffman EB, Gillman MW, Rifas-Shiman SL et al. Diagnostic accuracy of the bronchodilator response in children. J Allergy Clin Immunol. (2013) 132:554–9.e5. doi: 10.1016/j.jaci.2013.03.031
9. Global Initiative for Asthma. Global Strategy for Asthma Management Prevention. (2017). Available online at: www.ginasthma.org
10. NICE Guideline. (2017). Available online at: www.nice.org.uk/guidance/ng80
11. Fuhlbrigge AL, Kitch BT, Paltiel AD, Kuntz KM, Neumann PJ, Dockery DW et al. FEV1 is associated with risk of asthma attacks in a pediatric population. J Allergy Clin Immunol. (2001) 107:61–7. doi: 10.1067/mai.2001.111590
12. Schifano ED, Hollenbach JP, Cloutier MM. Mismatch between asthma symptoms and spirometry: implications for managing asthma in children. J Pediatr (2014) 165:997–1002. doi: 10.1016/j.jpeds.2014.07.026
13. Francisco B, Ner Z, Ge B, Hewett J, König P. Sensitivity of different spirometric tests for detecting airway obstruction in childhood asthma. J Asthma (2015) 52:505–11. doi: 10.3109/02770903.2014.984842
14. Quanjer PH, Weiner DJ, Pretto JJ, Brazzale DJ, Boros PW. Measurement of FEF25-75% and FEF75% does not contribute to clinical decision making. Eur Respir J. (2014) 43:1051–8. doi: 10.1183/09031936.00128113
15. Culver BH, Graham BL, Coates AL, Wanger J, Berry CE, Clarke PK et al. Recommendations for a standardized pulmonary function report. an official American thoracic society technical statement. Am J Respir Crit Care Med. (2017) 196:1463–72. doi: 10.1164/rccm.201710-1981ST
16. Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. (2014) 43:343–73. doi: 10.1183/09031936.00202013
17. Barsky EE, Giancola LM, Baxi SN, Gaffin JM. A Parctical Approach to Severe Asthma in Children. Ann Am Thorac Soc. (2017) 15:399–408. doi: 10.1513/AnnalsATS.201708-637FR
18. Guilbert TW, Bacharier LB, Fitzpatrick AM. Severe asthma in children. J Allergy Clin Immunol Pract. (2014) 2:489–500. doi: 10.1016/j.jaip.2014.06.022.
19. Fitzpatrick AM. Severe asthma in children: lessons learned and future di- rections. J Allergy Clin Immunol Pract. (2016) 4:11–9; quiz 20–1. doi: 10.1016/j.jaip.2015.10.008
20. Teague WG, Phillips BR, Fahy JV, Wenzel SE, Fitzpatrick AM, Moore WC et al. Baseline features of the Severe Asthma Research Program (SARP III) cohort: differences with age. J Allergy Clin Immunol Pract. (2018) 6:545–54.e4. doi: 10.1016/j.jaip.2017.05.032
21. Fitzpatric AM, Moore CW. Severe asthma phenotypes – How should they guide evaluation and treatment? J Allergy Clin Immunol Pract. (2017) 5:901–8. doi: 10.1016/j.jaip.2017.05.015.
22. Fitzpatrick AM, Teague WG, Meyers DA, Peters SP, Li X, Li H et al. Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program. J Allergy Clin Immunol. (2011) 127:382–89.e1–13. doi: 10.1016/j.jaci.2010.11.015
23. Coverstone A, Bacharier LB, Fitzpatrick AM. Severe asthma in school-age children: evaluation and phenotypic advances. Curr Allergy Asthma Rep. (2015) 15:20. doi: 10.1007/s11882-015-0521-5
24. Fitzpatrick AM, Gaston BM, Erzurum SC, Teague WG. Features of severe asthma in school-age children: atopy and increased exhaled nitric oxide. J Allergy Clin Immunol. (2006) 118:1218–25. doi: 10.1016/j.jaci.2006.08.019
25. Jenkins HA, Cherniack R, Szefler SJ, Covar R, Gelfand EW, Spahn JD. A comparison of the clinical characteristics of children and adults with severe asthma. Chest (2003) 124:1318–24. doi: 10.1378/chest.124.4.1318
26. Calhoun WJ, Haselkorn T, Miller DP, Omachi TA. Asthma exacerbations and lung function in patients with severe or difficult-to-treat asthma. J Allergy Clin Immunol. (2015) 136:1125–7.e4. doi: 10.1016/j.jaci.2015.05.014
27. Castro-Rodriguez JA, Saglani S, Rodriguez-Martinez CE, Oyarzun MA, Fleming L, Bush A. The relationship between inflammation and remodeling in childhood asthma: a systematic review. Pediatr Pulmonol. (2018) 53:824–35. doi: 10.1002/ppul.23968
28. Ortega H, Yancey SW, Keene ON, Gunsoy NB, Albers FC, Howarth PH. Asthma exacerbations associated with lung function decline in patients with severe eosinophilic asthma. J Allergy Clin Immunol Pract. (2018) 6:980–6.e1. doi: 10.1016/j.jaip.2017.12.019
29. Deschildre A, Marguet C, Salleron J, Pin I, Rittié JL, Dorelle J et al. Add-on omalizumab in children with severe allergic asthma: a 1-year real life survey. Eur Respir J. (2013) 42:1224–33. doi: 10.1183/09031936.00149812
30. Versiani Nunes Pinheiro de Queiroz M, Gonçalves AC, Cruz AA, de Lima Belizario Facury Lasmar LM. Lung function in severe pediatric asthma: a longitudinal study in children and adolescents in Brazil. Clin Transl Allergy (2017) 7:48. doi: 10.1186/s13601-017-0183-6
31. Labbe G, Merlin E, Kauffman C, Fauquert JL, Héraud MC, Labbé A. The role of lung volume measurements by plethysmography in the follow-up of asthma in children. Rev Mal Respir (2010) 27:42–8. doi: 10.1016/j.rmr.2009.11.002
32. Sorkness RL, Teague WG, Penugonda M, Fitzpatrick AM. Sex dependence of airflow limitation and air trapping in children with severe asthma. J Allergy Clin Immunol. (2011) 127:1073–4. doi: 10.1016/j.jaci.2010.12.1079
33. Bisgaard H, Nielsen KG. Plethysmographic measurements of specific airway resistance in young children. Chest (2005) 128:355–62. doi: 10.1378/chest.128.1.355
34. Merkus PJFM, Stocks J, Beydon N, Lombardi E, Jones M, McKenzie SA et al. Reference ranges for interrupter resistance technique: the Asthma UK Initiative. Eur Respir J (2010) 36:157–63. doi: 10.1183/09031936.00125009
35. Calogero C, Simpson SJ, Lombardi E, Parri N, Cuomo B, Palumbo M et al. Respiratory impedance and bronchodilator responsiveness in healthy children aged 2–13 years. Pediatr Pulmonol. (2013) 48:707–15. doi: 10.1002/ppul.22699
36. Kirkby J, Stanojevic S, Welsh L, Lum S, Badier M, Beardsmore C et al. Reference equations for specific airway resistance in children: the Asthma UK initiative. Eur Respir J. (2010) 36:622–9. doi: 10.1183/09031936.00135909
37. Nielsen KG, Bisgaard H. Discriminative capacity of bronchodilator response measured with three different lung function techniques in asthmatic and healthy children aged 2 to 5 years. Am J Respir Crit Care Med. (2001) 164:554–9. doi: 10.1164/ajrccm.164.4.2006119
38. Thamrin C, Gangell CL, Udomittipong K, Kusel MM, Patterson H, Fukushima T et al. Assessment of bronchodilator responsiveness in preschool children using forced oscillations. Thorax (2007) 62:814–9. doi: 10.1136/thx.2006.071290
39. Marotta A, Klinnert MD, Price MR, Larsen GL, Liu AH. Impulse oscillometry provides an effective measure of lung dysfunction in 4-year- old children at risk for persistent asthma. J Allergy Clin Immunol. (2003) 112:317–22. doi: 10.1067/mai.2003.1627
40. Song TW, Kim KW, Kim ES, Park JW, Sohn MH, Kim KE. Utility of impulse oscillometry in young children with asthma. Pediatr Allergy Immunol. (2008) 19:763–768. doi: 10.1111/j.1399-3038.2008.00734.x
41. Heijkenskjöld Rentzhog C, Janson C, Berglund L, Borres MP, Nordvall L, Alving K et al. Overall and peripheral lung function assessment by spirometry and forced oscillation technique in relation to asthma diagnosis and control. Clin Exp Allergy (2017) 47:1546–54. doi: 10.1111/cea.13035
42. Komarow HD, Skinner J, Young M, Gaskins D, Nelson C, Gergen PJ et al. A study of the use of impulse oscillometry in the evaluation of children with asthma: analysis of lung parameters, order effect, and utility compared with spirometry. Pediatr Pulmonol. (2012) 47:18–26. doi: 10.1002/ppul.21507
43. Saadeh C, Cross B, Gaylor M, Griffith M. Advantage of impulse oscillometry over spirometry to diagnose chronic obstructive pulmonary disease and monitor pulmonary responses to bronchodilators: an observational study. SAGE Open Med. (2015) 3:2050312115578957. doi: 10.1177/2050312115578957
44. Shi Y, Aledia AS, Galant SP, George SC. Peripheral airway impairment measured by oscillometry predicts loss of asthma control in children. J Allergy Clin Immunol. (2013) 131:718–23. doi: 10.1016/j.jaci.2012.09.022
45. Larsen GL, Morgan W, Heldt GP, Mauger DT, Boehmer SJ, Chinchilli VM. Impulse oscillometry versus spirometry in a long-term study of controller therapy for pediatric asthma. J Allergy Clin Immunol. (2009) 123:861–7.e1. doi: 10.1016/j.jaci.2008.10.036
46. Van Nederveen-Bendien SA, Vahl J, Heijerman HGM. Specific airway resistance is a better outcome parameter in bronchial provocation testing compared to FEV1 in patients with bronchial asthma. J Asthma (2018) 17:1–5. doi: 10.1080/02770903.2017.1414238
47. Ramsey KA, Rosenow T, Turkovic L, Skoric B, Banton G, Adams AM et al. Lung clearance index and structural lung disease on computed tomography in early cystic fibrosis. Am J Respir Crit Care Med. (2016) 193:60–7. doi: 10.1164/rccm.201507-1409OC
48. Weiler JM, Brannan JD, Randolph CC, Hallstrand TS, Parsons J, Silvers W et al. Exercise-induced bronchoconstriction update-2016. J Allergy Clin Immunol. (2016) 138:1292–95.e36. doi: 10.1016/j.jaci.2016.05.029
49. Coates AL, Wanger J, Cockcroft DW, Culver BH, Carlsen K-H Diamant Z et al. ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests. Eur Respir J. (2017) 49:1601526. doi: 10.1183/13993003.01526-2016
50. Park HW, Song WJ, Chang YS, Cho SH, Datta S, Weiss ST et al. Bronchodilator response following methacholine-induced bronchoconstriction predicts acute asthma exacerbations. Eur Respir J. (2016) 48:104–14. doi: 10.1183/13993003.00182-2016
Keywords: severe asthma, lung function, children, respiratory resistance, reactance
Citation: Calogero C, Fenu G and Lombardi E (2018) Measuring Airway Obstruction in Severe Asthma in Children. Front. Pediatr. 6:189. doi: 10.3389/fped.2018.00189
Received: 29 April 2018; Accepted: 07 June 2018;
Published: 26 June 2018.
Edited by:
Renato Cutrera, Bambino Gesù Ospedale Pediatrico (IRCCS), ItalyReviewed by:
Refika Ersu, Marmara University, TurkeyAhmad Kantar, University and Reserach Hospital - Istituti Ospedalieri Bergamaschi, Italy
Copyright © 2018 Calogero, Fenu and Lombardi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Enrico Lombardi, ZW5yaWNvLmxvbWJhcmRpQG1leWVyLml0